Tomographic magnetic particle imaging of cancer targeted nanoparticles

Magnetic Particle Imaging (MPI) is an emerging, whole body biomedical imaging technique, with sub-millimeter spatial resolution and high sensitivity to a biocompatible contrast agent consisting of an iron oxide nanoparticle core and a biofunctionalized shell. Successful application of MPI for imaging of cancer depends on the nanoparticles (NPs) accumulating at tumors at sufficient levels relative to other sites. NPs' physiochemical properties such as size, crystallographic structure and uniformity, surface coating, stability, blood circulation time and magnetization determine the efficacy of their tumor accumulation and MPI signal generation. Here, we address these criteria by presenting strategies for the synthesis and surface functionalization of efficient MPI tracers, that can target a typical murine brain cancer model and generate three dimensional images of these tumors with very high signal-to-noise ratios (SNR). Our results showed high contrast agent sensitivities that enabled us to detect 1.1 ng of iron (SNR similar to 3.9) and enhance the spatial resolution to about 600 mu m. The biodistribution of these NPs was also studied using near-infrared fluorescence (NIRF) and single-photon emission computed tomography (SPECT) imaging. NPs were mainly accumulated in the liver and spleen and did not show any renal clearance. This first preclinical study of cancer targeted NPs imaged using a tomographic MPI system in an animal model paves the way to explore new nanomedicine strategies for cancer diagnosis and therapy, using clinically safe magnetic iron oxide nanoparticles and MPI.